Up-regulation of the IFN-γ pathway in the absence of TC-PTP. The loss of TC-PTP results in increased activation of the IFN-γ pathway through hyperphosphorylation of JAK1¹  and STAT1.³  STAT1 activity induces TNF-α and iNOS expression. LPS increases IL-18 production, which together with IL-12 serves as a positive feedback to IFN-γ-producing cells. In the absence of TC-PTP this cycle cannot be turned off and results in the accumulation of IFN-γ, TNF-α, NO, and activated inflammatory cells.